EMPHYSEMA

Pathology Notes - 2nd Year | ABVM University

1. INTRODUCTION

• It is one of the two major components of Chronic Obstructive Pulmonary Disease (COPD), the other being chronic bronchitis.
• Clinically significant obstruction occurs when respiratory bronchioles collapse during expiration due to loss of elastic recoil from destroyed alveolar walls.
• The lobule is a cluster of acini (terminal respiratory units); emphysema is classified by which segment of the acinus is affected.

2. LOCATION

• Centriacinar - Upper lobes predominant, particularly apical segments; most common in smokers
• Panacinar - Lower zones and anterior margins; severe at the lung bases; associated with alpha-1 antitrypsin (AAT) deficiency
• Paraseptal (Distal acinar) - Adjacent to the pleura, along lobular connective tissue septa; upper half of lungs; near areas of fibrosis or atelectasis
• Irregular (Paracicatricial) - Anywhere, always associated with areas of scarring; usually small foci

3. ETIOLOGY

• Responsible for the vast majority of clinically significant emphysema
• Causes toxic injury, inflammation, protease release, and oxidative stress to respiratory epithelium
• Nicotinic acetylcholine receptor variants may influence smoking addictiveness and thus lung cancer/emphysema risk

• Congenital deficiency of the antiprotease AAT
• Leads to unopposed protease activity in the lung
• Causes panacinar emphysema; greatly exacerbated by smoking
• AAT is encoded on chromosome 14 (Pi locus); the severe Z allele produces a misfolded protein retained in hepatocytes

• Air pollutants and dust (grain, cotton, silica)
• Repeated pulmonary infections may acutely exacerbate existing disease (though not initiating)
• Other genetic variants linked to emphysema risk have been identified

4. PATHOGENESIS

Step-by-step mechanism:

• Inhaled smoke/noxious particles damage respiratory epithelium
• Resident epithelial cells and macrophages release inflammatory mediators: LTB4, IL-8, TNF, and others
• These mediators attract inflammatory cells (neutrophils, macrophages), amplify inflammation, and induce structural changes
• Chronic inflammation accumulates T and B lymphocytes in affected lung

• Neutrophils and macrophages release proteases (mainly elastase, matrix metalloproteinases - MMPs) that break down connective tissue (elastin, collagen)
• Protective antiproteases are relatively deficient - in some patients this is genetic (AAT deficiency)
• Unchecked protease activity destroys alveolar walls

• Tobacco smoke, alveolar damage, and inflammatory cells all produce reactive oxygen species (ROS)
• Oxidants cause direct tissue damage, endothelial dysfunction, and amplify inflammation
• NRF2 (encoded by NFE2L2) normally protects cells from oxidant damage; its impairment worsens susceptibility
• Mice lacking NRF2 are markedly more sensitive to tobacco smoke

• Destruction of alveolar walls reduces elastic tissue
• Small airways lose radial traction from surrounding parenchyma
• Airways collapse during expiration → functional airflow obstruction

• Bacterial/viral infections do not initiate destruction but acutely worsen existing disease

5. TYPES - COMPARATIVE TABLE

6. GROSS AND MICROSCOPIC FEATURES

Gross (Macroscopic) Appearance

• Voluminous, overinflated lungs - Lungs overlap the heart anteriorly on gross examination
• Flattened diaphragm - Due to air trapping and hyperinflation
• Large visible alveoli on the cut surface of fixed lungs
• Apical blebs and bullae - Characteristic of irregular (paraseptal) emphysema; prominent in advanced disease; bullae are air spaces >1 cm in diameter
• Upper two-thirds of lungs more severely affected in smoking-related disease

Microscopic (Histological) Appearance

• Abnormally large, dilated alveoli separated by thin septa
• Focal centriacinar fibrosis within the thin septa
• Loss of alveolar wall attachments to the outer wall of small airways
• Enlarged pores of Kohn - So large that the septa appear to be "floating" or protruding blindly into alveolar spaces with club-shaped ends
• Decreased capillary bed area due to alveolar wall destruction
• In advanced disease: even larger abnormal airspaces, bullae that compress respiratory bronchioles and vasculature
• Superimposed inflammatory changes in small airways (from coexisting chronic bronchitis)
• Vascular changes of pulmonary hypertension - Due to local hypoxemia and loss of capillary beds

7. CLINICAL FEATURES

• Progressive exertional dyspnea - The dominant complaint; insidious onset
• Minimal or no cough (in pure emphysema, unlike chronic bronchitis)
• Little to no sputum production
• Weight loss in advanced disease

• Barrel chest - Increased AP diameter from air trapping
• Pursed-lip breathing - Maintains positive end-expiratory pressure to prevent airway collapse
• Accessory muscle use
• Prolonged expiratory phase
• Relatively well-oxygenated (pink) due to increased respiratory effort maintaining PaO2
• Tachypnea (rapid breathing rate)

• Hyperresonance on percussion
• Diminished breath sounds bilaterally
• Decreased chest expansion
• Low, flat diaphragm (seen on CXR)

• Spontaneous pneumothorax - Especially with paraseptal/bullous emphysema when a bulla ruptures
• Pulmonary hypertension - From hypoxic vasoconstriction and capillary bed loss
• Cor pulmonale (right heart failure) - From chronic pulmonary hypertension
• Secondary polycythemia - From chronic hypoxemia stimulating erythropoietin
• Respiratory failure in end-stage disease

• Reduced FEV1/FVC ratio (<70%) - Obstructive pattern
• Increased TLC, RV (air trapping)
• Reduced DLCO (diffusing capacity) - Due to loss of alveolar-capillary surface area

Exam Tip: Remember that only Centriacinar and Panacinar types cause clinically significant airflow obstruction. Paraseptal causes spontaneous pneumothorax; Irregular is usually clinically silent. The key mechanism is protease-antiprotease imbalance - always highlight this in exams.

• Robbins, Cotran & Kumar Pathologic Basis of Disease, pp. 635-636